IN the NEWS: Bardoxolone Methyl and CKD

A new agent called Bardoxolone( anti oxidant) , also called BARD in the prior literature, was studied in a recent NEJM 2011 paper in close to 200 adults with CKD in a randomized, double blinded placebo controlled phase 2 trial. Doses used were 25, 75 or 150mg. The outcomes were change in GFR at 6 months and 1 year.  The results showed that patients who received the agent had statistically more significant GFR increases compared to placebo- all which were maintained at 1 year.  The increases were in the magnitude of 9-10ml.  Low Mg levels and muscle spasms were side effects noted.  
Few years prior, studies had shown that BARD ameliorated ischemic murine AKI as assessed by both renal function and pathology. It is possible that BARD does this by effects on  NF-E2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor-γ (PPARγ), and heme oxygenase 1 (HO-1).  Studies have shown that BARD regulates PPARγ, not by acting as a ligand but by increasing the amount of PPARγ mRNA and protein.  Prior results  also found that BARD ameliorated cisplatin nephrotoxicity. So it was an inflammation modulator.  Following that there was a shorter study in AJ Nephrology listed below that showed benefit with BARD in CKD stage 3b and 4.


Ref:
http://www.ncbi.nlm.nih.gov/pubmed/21289052
http://www.ncbi.nlm.nih.gov/pubmed/21508635
http://www.nejm.org/doi/full/10.1056/NEJMoa1105351?query=featured_home